Project Summary Injuries to the anterior cruciate ligament (ACL) are highly debilitating; each year they affect more than 120,000 individuals in the United States and 1.4 million worldwide. It is estimated that one-third of these individuals will suffer subsequent truama of the same kind to the contralateral knee or ACL graft. Not only do these injuries result in time lost from sport and activity, are immediatley disabeling, and typically require surgery, they are associated with post traumatic osteoarthritis (PTOA) of the knee regardless of the type of treatment that is chosen. ACL injury and the subsequent sequela of PTOA is debilitating due to its earlier onset in comparison to idiopathic osteoarthritis (OA), creating a considerable therapeutic concern as a majority of these injuries occur in active young individuals between 15 and 25 years of age that place high demand on their joints and consequently require earlier and more frequent surgery and rehabilitation. During the prior funding interval, we determined the risk factors for a first time ACL tear (please see Progress Report for details). A subset of the injured athletes from that study were followed after surgery, rehabilitation and return to sport for 2 years, and 18% went on to suffer a complete disruption of their contralateral ACL (CACL), and 10.9% suffered a graft injury (total re-injury rate of 28.9%). Rather than treat this trauma and the subsequent burden of PTOA though surgical approaches, which are only marginally successful, a more proactive approach is to identify individuals at increased risk of suffering ACL injury and develop injury prevention programs to mitigate that risk. The investigation in this application is focused on establishing a complete understanding of the risk factors for a CACL injury. This is an essential next step for understanding why these injuries occur, the development of prevention strategies that take prior ACL injury into account, and for identifying those that are at the greatest risk of suffering repeated ACL trauma so they can be targeted for injury prevention interventions. The goal of this investigation will be to determine the comprehensive set of risk factors associated with suffering a CACL following recovery form a first time ACL injury and return to sport/activity. This will be accomplished by executing the following Specific Aims: 1. To prospectively identify and recruit high school and college athletes who suffer a first-time ACL injury. 2. To measure a comprehensive set of potential risk factors for subsequent CACL injury at the time of the athlete's return to sport/activity following treatment and rehabilitation. These will include anatomic, strength and neuromuscular measurements on the contralateral leg, and clinical, demographic, and environmental factors. 3. To follow study subjects over time to identify subsequent non-contact injury to the CACL. 4. To determine combinations of risk factors that are associated with the risk of suffering a CACL injury in males and females.